Understanding immunity and host-microbe interactions in the female genital tract

The female genital tract (FGT) is a critical but understudied immune barrier that must protect against sexually transmitted infections while tolerating commensal microbes and supporting reproduction. To define the fundamental immunology of the FGT, we are generating high-resolution maps of immune cell composition and function using spatial transcriptomics and single-cell RNA sequencing. We are characterizing antigen-specific T and B cells to understand how adaptive repertoires are shaped during health and disrupted in bacterial vaginosis (BV).

We also study how microbial metabolites modulate immune function, how BV alters adaptive immunity, and how microbial metabolic machinery complements host pathways to maintain epithelial and immune homeostasis. Longitudinal studies capture how temporal changes in vaginal microbiome composition influence immunity and disease risk. Finally, we are probing the earliest immune responses to acute HPV and HIV infections to reveal mechanisms of susceptibility and inform new strategies for prevention and intervention.

Characterizing HIV disease progression in the gut

Despite effective antiretroviral therapy, people living with HIV continue to experience persistent dysregulation and chronic inflammation in the gut, which contributes to comorbidities that reduce quality of life and increase long-term complications. In the Kwon Lab, we investigate the cellular and metabolic mechanisms driving this gut dysregulation. Using primary human cells, we generate colonic organoids, miniaturized models of the colon, to study how epithelial and immune cells respond to HIV-associated stressors and how their metabolic programs are altered. These studies reveal how HIV disrupts intestinal homeostasis and points toward strategies to restore balance.

In parallel, we examine the systemic consequences of gut inflammation, with a particular focus on cardiovascular disease. Through mouse models, we evaluate how HIV-induced gut dysfunction promotes processes such as atherosclerotic plaque development. Together, these approaches provide an integrated view of how HIV impacts gut health and its downstream effects on other organ systems.

From vaginal microbiome discovery to diagnostics and interventions

Given the profound impact of the vaginal microbiome on reproductive and infectious disease outcomes, strategies to modulate microbial communities toward a more health-associated state represent a key research priority. Our work focuses on leveraging naturally occurring metabolites to selectively promote the growth of anti-inflammatory bacterial species while suppressing those associated with BV, with the goal of developing effective non-antibiotic treatments for BV.

In parallel, we are building genetic tools to engineer Lactobacillus crispatus, a dominant anti-inflammatory vaginal microbe. These tools will enable mechanistic studies of how L. crispatus grows, persists, and interacts with the host environment in the FGT, ultimately informing new approaches to enhance its colonization and stability in individuals at risk for BV. Together, these efforts aim to establish novel strategies for durable microbiome modulation to improve women’s health.